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Measurement of Lifespan in Drosophila melanogaster
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Longevity GWAS Using the Drosophila Genetic Reference Panel.

Dobril K Ivanov1, Valentina Escott-Price2, Matthias Ziehm3

  • 1European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge, UK. divanov@ebi.ac.uk.

The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
|April 30, 2015
PubMed
Summary
This summary is machine-generated.

Genetic variation significantly impacts fruit fly lifespan, with common genetic markers explaining a small portion of this variation. Key genes involved in metabolism and cell death pathways are implicated in aging processes.

Keywords:
AgeingGene ontologyGene-based analysisInsulin signaling pathwayPolygenic score analysisTarget of rapamycin

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Area of Science:

  • Genetics
  • Aging Research
  • Molecular Biology

Background:

  • Lifespan exhibits significant natural variation within populations.
  • Understanding the genetic underpinnings of this variation is crucial for aging research.

Purpose of the Study:

  • To conduct a genome-wide association study (GWAS) for virgin female lifespan in Drosophila melanogaster.
  • To identify genetic variants and pathways contributing to natural variation in lifespan.

Main Methods:

  • Utilized the Drosophila melanogaster Genetic Reference Panel (DGRP) with 197 lines.
  • Performed genome-wide association analysis using approximately 2 million common single nucleotide polymorphisms (SNPs).
  • Employed polygenic score analysis and pathway enrichment analyses (Gene Ontology, InterPro).

Main Results:

  • Broad-sense heritability of lifespan was estimated at 0.413, indicating substantial genetic influence.
  • Polygenic score analysis explained ~4.7% of lifespan variation through additive effects of common SNPs.
  • Identified top-associated genes involved in carbohydrate metabolism, cell death, and proteolysis.
  • The target of rapamycin (TOR) pathway showed significant enrichment among top-ranked genes.
  • Genes related to carbohydrate metabolism, including DUF227, were highlighted for their importance in lifespan determination.

Conclusions:

  • Natural variation in lifespan is influenced by a complex genetic architecture, with common SNPs playing a role.
  • The study highlights the importance of carbohydrate metabolism and the TOR pathway in aging.
  • Identified novel candidate genes for future experimental investigation into lifespan regulation.